Normalizing or reduction of the abnormal permeability of persons having capillar fragility with para-di-hydroxybenzene sulfonate



United States Patent U.S. Cl. 424-316 6 Claims ABSTRACT OF THE DISCLOSURE Process of acting on the vascular wall of the blood system of ill persons to normalize the capillar fragility, or to reduce the abnormal permeability of the wall, by administering compounds of the formula:

I OH

R in the above formula may be sodium, calcium, ammonium, alkylammonium, or alkanolammonium.

This application is a continuation-in-part of application Ser. No. 329,391, filed Dec. 10, 1963, now Patent No. 3,351,526, and application Ser. No. 202,981, filed June 18, 1962, now Patent No. 3,354,201, the latter of which is a continuation-in-part of application Ser. No. 2, filed J an. 4, 1960, now abandoned.

The present invention concerns a process of acting on the vascular wall of the blood system of ill persons, by

making the capillar fragility become normal or by reducing an abnormal permeability of the wall.

According to the invention, said process comprises administering to said persons compounds of the formula in which R is selected from the group consisting of sodium, calcium, ammonium, alkylammonium and alkanolammonium.

It has been found, that among the compounds having said general formula, sodium para-dihydroxybenzene sulfonate, calcium para-dihydroxybenzene sulfonate, ammonium para-dihydroxybenzene sulfonate, diethyl ammonium para-dihydroxybenzene sulfonate, and triethanolammonium para-dihydroxybenzene sulfonate are especially suitable for acting on the vascular wall by making its fragility become normal or by reducing its permeability, when such fragility or permeabilit are abnormally high.

The compounds may be administered e.g. intramuscularly or intravenously (injectable solutions of 2 cc. with 250 mg. of active principle), per os in capsules of 250 mg, or even rectally with suppositories dosed at 500 mg.

EXAMPLE 1 To a group of patients of different ages and sex, having a very high increase in capillary fragility, injection of a single .dose of 0.250 g. to 1 g. of diet'hylammonium para- Patented Apr. 1, 1969 dihydroxybenzene sulfonate was made. This injection causes the fragility to become normal in 70% of all cases, whereas with the other patients an increase in vascular resistance of the order of 50 to could be observed.

These effects persist for two days and more, whereafter they diminish slowly during five or six days to values clearly inferior of the initial ones. This shows that the effects are not due to a mere vaso-constrictorial action.

To another group of patients, which had similar alterations of the capillar fragility, were given during two days eight tablets per day containing each 250 mg. of diethylammonium para-dihydroxybenzene sulfonate. Thereby, substantially the same results were obtained as with the above-mentioned injection.

EXAMPLE 2 In a group of patients, local hyperaemia is caused by applying an ointment of 5% tetrahydrofurfurylic ester of nictotinic acid to forearm skin. When these patients had received an intramuscular injection of 500 mg. of diethylammonium para-dihydroxybenzene sulfonate an hour before the same test had been repeated to the other forearm, it couldbe seen that the surface of the hyperaemia area was reduced by 45% with respect to the control test.

The method for obtaining exact results with these tests comprises putting a dye on the hyperaemia surface, and transferring thereafter this dye spot to a millimeter paper, by direct contact. Thus, the surface of the dye spot can be measured with great precision. The comparison of the dye spot surfaces of the right and left forearm respectively (before and after administering the product) permits to determine exactly the percentage of the diminution.

A similar diminution is obtained if the patients receive either 16 tablets of 250 mg. of said product in a.

rhythm of two tablets each sixth hour, or one suppository containing 500 mg. of said product four times a day during two days.

EXAMPLE 3 EXAMPLE 4 In another group of patients, local hyperaemia is caused by applying an ointment of 5% tetrahydrofurfurylic ester of nicotinic acid to forearm skin. When these patients had received an intramuscular injection of 500 mg. of ammonium para-dihydroxybenzene sulfonate an hour before the same test had been repeated to the other forearm skin, it could be seen that the surface of the hyperaemia area was reduced by 14.4 to 44.7%, the mean value being 30%.

A similar diminution is obtained if the patients receive either 16 tablets of 250 mg. of said product in a rhythm of two tablets each sixth hour, or one suppository containing 500 mg. of said product four times a day during two days.

The results of Example 1 clearly demonstrate that the above-mentioned chemicals normalize capillar fragility when it has become abnormal for some reason or other. Likewise, Examples 2, 3 and 4 show that the vascular permeability remains reduced if one of the above-mentioned chemicals is applied.

The sodium and calcium salt of para-dihydroxybenzene sulfonate were tested as described in Examples 1 to 4 above, and results very similar to those mentioned in 3 these four examples had been obtained with said sodium and calcium salt.

What I claim is:

1. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of a compound of the formula I OH ' comprises administering to said person an effective amount of calcium para-dihydroxybenzene sulfonate.

4. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of ammonium para-dihydroxybenzene sulfonate.

5. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of diethylammonium para-dihydroxybenzene sulfonate.

6. A method of normalizing or reducing the abnormal permeability of a person having capillar fragility which comprises administering to said person an effective amount of triethanolammonium para-dihydroxybenzene sulfonate.

References Cited Chem. Abst., 60:1652h-1653a, 1964.

ALBERT T. MEYERS, Primary Examiner.

S. J. FRIEDMAN, Assistant Examiner.

U.S. Cl. X.R. 424315 

